Structure and topology of Slc11a1(164-191) with G169D mutation in membrane-mimetic environments.
Solute carrier family 11 member 1 (Slc11a1) is a proton-mediated divalent metal cation transporter with 12 putative transmembrane domains. Variation in it reveals alterations in host resistance against intracellular pathogens. A naturally occurring glycine to aspartic acid mutation at position 169 (G169D) in the putative transmembrane domain 4 (TM4) makes mice susceptible to Salmonella typhimurim, Leishmania donovani, and Mycobacterium bovis. In this work, a 28-residue peptide corresponding to Slc11a1(164-191), including TM4 of Slc11a1, with G169D mutation is characterized using CD and NMR methods in 2,2,2-trifluoroethanol solvent and SDS micelles and the results of present study on the G169D peptide are compared with those of previous study on the wild-type peptide. Similarly to the wild-type peptide, the G169D peptide forms a predominantly alpha-helical structure and is totally embedded in SDS micelles as a homologous assembly. However, the G169D mutation changes the local conformation near the mutation site, the cooperative manner in proton binding of the residue Asp located in the center of SDS micelles and the interaction strength of this residue with Mn2+ ions.
Xue
Rong
R
State Key Laboratory of Supramolecular Structure and Materials, Jilin University, 2699 Qianjin Avenue, Changchun, Jilin 130012, People's Republic of China.
Wang
Shuo
S
Qi
Haiyan
H
Song
Yuande
Y
Xiao
Shuyan
S
Wang
Chunyu
C
Li
Fei
F
D019943:Amino Acid Substitution; D000818:Animals; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics*; D002942:Circular Dichroism; D051379:Mice; D008823:Micelles; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D014270:Trifluoroethanol / Q000737:chemistry; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D008823:Micelles; D010455:Peptides; D012967:Sodium Dodecyl Sulfate; D014270:Trifluoroethanol; D000099173:Natural Resistance-associated Macrophage Protein 1